Small-animal positron emission tomography (PET) scanners have become an important technology in studying tumorigenesis, tumor growth and response to therapy in appropriate animal models of cancer, and for evaluating new agents being developed for molecularly-specific diagnostic imaging. This proposal brings together a new photodetector technology, position-sensitive solid state photomultipliers (SSPMs), with highly segmented scintillator arrays, to create a depth-encoding detector that will permit the design of a much higher sensitivity small-animal PET scanner, whilst maintaining spatial resolution and without increasing the complexity of the system in terms of number of channels of electronics. SSPMs combine the advantages of photomultiplier tubes (high gain and fast timing) with the advantages of avalanche photodiodes (thin cross-section, higher quantum efficiency, magnetic field tolerance) and thus offer an attractive opportunity for PET imaging. The two technological innovations in this proposal are the creation of large-area position-sensitive SSPMs, allowing multiplexed readout of many SSPMs with a small number of electronic channels, and the fact that the SSPMs are produced by a standard CMOS process that is easily scaleable and also allows incorporation of other electronic components right on the detector chip. By using position-sensitive SSPMs on either end of finely segmented scintillator arrays, depth-encoding detector modules can be designed that simultaneously offer very high spatial resolution and very high efficiency. This leads to PET scanner designs for small-animal imaging that have much higher sensitivity, without increasing the number of detector modules compared with current state-of-the-art systems. The significance of this proposal is that it offers a cost-effective pathway to much higher sensitivity PET imaging without degrading spatial resolution. This sensitivity improvement can be used to increase signal-to-noise, increase temporal resolution or decrease administered dose. This will be critical in many cancer applications, for example, allowing improved imaging and quantification of less abundant molecular targets, detection of smaller number of cells in cellular therapies and detection of smaller changes in radiotracer accumulation in response to interventions. [unreadable] [unreadable] PUBLIC HEALTH RELEVANCE: This proposal seeks to develop a highly sensitive positron emission tomography (PET) scanner for preclinical studies of new therapeutic and diagnostic cancer agents in mouse models of human cancer. This translational technology platform will help better identify appropriate new therapeutic and diagnostic agents to move into human clinical trials and may reduce the time and cost of bringing these new agents to the clinic. [unreadable] [unreadable] [unreadable]